D'Almeida V, Camarini R, Azzalis L A, Mattei R, Junqueira V B, Carlini E A
Department of Biochemistry, Universidade de São Paulo, Brazil.
Toxicol Lett. 1995 Nov 15;81(2-3):101-5. doi: 10.1016/0378-4274(95)03408-0.
Mazindol (5-hydroxy-5-p-chlorophenyl-2,3-dihydro-5H-imidazo-2,1-a-isoindole) although not chemically related to the phenylethylamine group, shows a pharmacological profile similar to that of amphetamines. In rats these anorectic drugs enhance dopamine (DA) turnover, which is the mechanism that causes anorexia. It has been hypothesized that amphetamine causes a long-lasting depletion of DA, a decrease of dopaminergic transport pumps and nerve terminal degeneration increasing. These actions provide a cellular environment encouraging the autoxidation of DA that may lead to lipid peroxidation and neuronal damage. Considering that both drugs may cause neuronal damage by oxidative mechanisms, this study was conducted to investigate the action of mazindol and methamphetamine on brain cell antioxidant defense system and to investigate whether animal age is important in the antioxidant response to chronic anorectic administration. The activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), as well as the total glutathione (GSH) content in brains of rats, were measured. The animals (2 groups with 5 and 18 months old) were treated for 5 months (i.p.) with mazindol (10 mg/kg body weight/day), methamphetamine (2.5 mg/kg body weight/day) or saline. The results obtained showed no differences between SOD, CAT, GPx activities and GSH content in the brain of animals treated with saline compared with both drugs, either in 10-month or 23-month groups. On the other hand, brain total GSH content of old animals was found to be lower than that from young ones, independent of the treatment. SOD activity was found to be increased, CAT unchanged and GPx decreased, in the brain of old animals, treated with both drugs or saline. These findings led us to conclude that the chronic administration of mazindol and methamphetamine have no effects on the antioxidant systems studied either in young (10 months) or in old (23 months) rats.
马吲哚（5-羟基-5-对氯苯基-2,3-二氢-5H-咪唑并[2,1-a]异吲哚）虽然在化学结构上与苯乙胺类无关，但却表现出与苯丙胺类相似的药理特性。在大鼠中，这些食欲抑制药物会增强多巴胺（DA）的代谢周转，这就是导致厌食的机制。据推测，苯丙胺会导致DA的长期耗竭、多巴胺能转运泵的减少以及神经末梢变性增加。这些作用提供了一个促使DA自氧化的细胞环境，而DA自氧化可能会导致脂质过氧化和神经元损伤。鉴于这两种药物都可能通过氧化机制导致神经元损伤，本研究旨在探究马吲哚和甲基苯丙胺对脑细胞抗氧化防御系统的作用，并研究动物年龄在对抗慢性食欲抑制药物给药的抗氧化反应中是否重要。我们测量了大鼠大脑中超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPx）的活性，以及总谷胱甘肽（GSH）的含量。将动物（两组，分别为5个月和18个月大）腹腔注射给予马吲哚（10毫克/千克体重/天）、甲基苯丙胺（2.5毫克/千克体重/天）或生理盐水，持续5个月。所得结果表明，在10个月龄组或23个月龄组中，与给予两种药物的动物相比，给予生理盐水的动物大脑中SOD、CAT、GPx活性以及GSH含量均无差异。另一方面，发现老年动物大脑中的总GSH含量低于年轻动物，且与治疗无关。在用两种药物或生理盐水处理的老年动物大脑中，发现SOD活性增加、CAT活性不变、GPx活性降低。这些发现使我们得出结论，长期给予马吲哚和甲基苯丙胺对年轻（10个月）或老年（23个月）大鼠所研究的抗氧化系统均无影响。
